Preparation method of 16a-hydroxy prednisolone acetate product

A technology of prednisolone hydroxyacetate and prednisone hydroxyacetate, which is applied in the direction of steroids and organic chemistry, can solve the problems of high impurities, low yield, and many side reactions in oxidation reactions, and achieve high yield and low impurity Less, the effect of reducing the production cost

Inactive Publication Date: 2019-05-10
HUNAN KEREY BIOTECH
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Therefore, the present invention aims at the problems of many side reactions of oxidation reaction and low yield of impurities in the traditional 16a-hydroxyprednisolone and 16a-hydroxyprednisolone acetate production process, in order to prepare 16a-hydroxyprednisolone efficiently and environmentally friendly Songlong and 16a-hydroxyacetate prednisolone, in the present invention, adopt earlier to prepare 16a-hydroxyacetate prednisolone with specific method first, then obtain by the method for alkaline hydrolysis of 16a-hydroxyacetate prednisolone under specific conditions 16a-Hydroxyprednisolone

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of 16a-hydroxy prednisolone acetate product
  • Preparation method of 16a-hydroxy prednisolone acetate product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] A. Preparation of oxides:

[0033] In a 5000ml three-necked flask, add 100g of 17-dehydroxyacetate prednisone, 2000ml of acetone, 12.5g of 80% formic acid, stir to dissolve the solid completely, control the temperature to 20-25°C, and add 900g of 5% dropwise within 1-1.5 hours Potassium permanganate aqueous solution, after dripping, react at 20-25°C for 1-2 hours, TLC controls the reaction end point, after the reaction, 90-95% of the solvent acetone is recovered by vacuum distillation below 35°C for the next Batch oxidation reaction, the residue was cooled to room temperature, added 1000ml of pure water for water analysis, filtered to obtain the oxide: crude product of 16a-hydroxyacetate prednisone; the crude product was recrystallized with 1000ml of 50% alcohol aqueous solution to obtain 16a-hydroxyacetate Nisone 93.8g, HPLC content 97.5%, weight yield about 93.8%;

[0034] B. Preparation of protection:

[0035] In a 1000ml three-neck flask, add 100g of the oxide pre...

Embodiment 2

[0042] A. Preparation of oxides:

[0043] In a 5000ml three-necked flask, add 100g of 17-dehydroxyacetate prednisone, 1500ml of chloroform, 15g of 20% phosphoric acid, stir to dissolve the solid completely, control the temperature to 20-25°C, and add 1500g of 3% phosphoric acid dropwise within 1-1.5 hours Potassium permanganate aqueous solution, after dripping, react at 20-25°C for 1-2 hours, TLC controls the reaction end point, after the reaction, recover 90-95% of the solvent chloroform by vacuum distillation below 35°C for the next batch Oxidation reaction, the residue was cooled to room temperature, added 1000ml of pure water for water analysis, filtered to obtain the oxide: 16a-hydroxyprednisone acetate crude product; the crude product was recrystallized with 1000ml50% alcohol aqueous solution to obtain 16a-hydroxyprednisone acetate Pine 91.6g, HPLC content 98.0%, weight yield about 91.6%;

[0044] B. Preparation of protection:

[0045] In a 1000ml three-neck flask, add...

Embodiment 3

[0052] A. Preparation of oxides:

[0053]In a 5000ml three-neck flask, add 100g of 17-dehydroxyprednisone acetate, 1500ml of DME, 50g of 20% acetic acid, stir to dissolve the solid completely, control the temperature to 20-25°C, and dropwise add 900g of 5% acetic acid within 1-1.5 hours Potassium manganate aqueous solution, after dripping, react at 20-25°C for another 1-2 hours, TLC controls the reaction end point, after the reaction, 90-95% of the solvent DME is recovered by vacuum distillation below 35°C for the next batch oxidation Reaction, the residue is cooled to room temperature, add 1000ml pure water for water analysis, filter to obtain the oxide compound: 16a-hydroxy prednisone acetate crude product; the crude product is recrystallized with 1000ml50% alcohol aqueous solution to obtain 16a-hydroxy prednisone acetate 92.5g, HPLC content 97.6%, weight yield about 92.5%;

[0054] B. Preparation of protection:

[0055] In a 1000ml three-neck flask, add 100g of the oxide ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

A preparation method of a 16a-hydroxy prednisolone acetate product includes dissolving 17-dehydroxy prednisone acetate as a raw material in an organic solvent, oxidizing 16 and 17 double bonds by potassium permanganate under acid catalysis to obtain an oxide, dissolving the obtained oxide in an organic solvent, adding acetone, and carrying out acid catalyzed reaction to obtain a protector; dissolving the protector in an organic solvent, adding a reducing agent to reduce ketone at the 11th position, directly adding an acid water solution for hydrolysis and deprotection after the reduction reaction to obtain 16a-hydroxy prednisolone acetate, and subjecting the crude product to decoloration and recrystallization by low-carbon-alcohol heating reflux to obtain the 16a-hydroxy prednisolone acetate product. Although two reaction steps, protection and deprotection, are added, the reaction yield of units in each step is high, the method is simple and convenient to operate, the process is economical and environmentally friendly, and the total synthesis yield is increased remarkably; the preparation cost of the preparation method is 20-25% lower than that of conventional production methods.

Description

technical field [0001] The invention belongs to the preparation technology of steroid hormone drug intermediates, and specifically relates to a key intermediate 16a- The preparation technology of prednisolone hydroxyacetate product. Background technique [0002] 16a-prednisolone hydroxyacetate (molecular formula C23H28O7), chemical name 11b, 16a, 17a, 21-tetrahydroxy-pregna-1,4-diene-3,20-dione, 21 acetate, is a A key intermediate for the production of neide steroid adrenocorticotropic hormone drugs, using it as a raw material, one-step condensation reaction with acetone to produce desonide acetate, one-step condensation with n-butyraldehyde to produce budesonide acetate, its hydrolysis After that, desonide and budesonide were prepared respectively. The steroid adrenocorticotropic hormone drug of neide is a kind of potent local anti-inflammatory agent. For example, budesonide is mainly used for various rhinitis, acute and chronic bronchitis clinically. The treatment of man...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07J5/00
Inventor 胡爱国谢来宾羊向新
Owner HUNAN KEREY BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap